Risk of Adverse Cardiovascular Events With Proton Pump Inhibitors Independent of Clopidogrel

Systematic Review With Meta-analysis

Riley Batchelor; Radya Kumar; Julia F. M. Gilmartin-Thomas; Ingrid Hopper; William Kemp; Danny Liew

Disclosures

Aliment Pharmacol Ther. 2018;48(8):780-796. 

In This Article

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Supplement 2: Ovid MEDLINE Search Strategy

Database: Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) <1946 to Present>Search date: 04/10/2017

  1. exp proton pump inhibitors/(17178)

  2. exp H+-K+-Exchanging ATPase/(1587)

  3. exp 2-Pyridinylmethylsulfinylbenzimidazoles/(10994)

  4. anti-ulcer agents/or dexlansoprazole/or esomeprazole/or lansoprazole/or omeprazole/or rabeprazole/(18933)

  5. antacids/(6381)

  6. gastroesophageal reflux/dt (4397)

  7. proton pump inhib*.tw. (12039)

  8. (hydrogen potassium atpase adj2 (block* or inhib* or antagon*)).tw. (5)

  9. (potassium competitive acid adj2 (block* or inhib* or antag*)).tw. (105)

  10. proton pump antagon*.tw. (9)

  11. proton pump block*.tw. (49)

  12. (prilosec or nexium or protonix).tw. (117)

  13. antacid*.tw. (4584)

  14. ((antiulcer or anti ulcer or anti-ulcer or antisecretory or anti secretory or anti- secretory) adj (drug* or agent* or medication*)).tw. (2788)

  15. (omeprazol* or esomeprazol* or rabeprazol* or dexlansoprazol* or ilaprazol* or benatoprazol* or leminoprazol* or picoprazole* or pumaprazol* or timoprazol* or saviprazol* or tenatoprazol* or pantoprazol*).mp. (13587)

  16. (gastric acid adj (suppress* or inhib* or block*)).tw. (641)

  17. PPI*.tw. (18799)

  18. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 (54922)

  19. cardiovascular diseases/or exp heart diseases/or vascular diseases/or arterial occlusive diseases/or exp arteriosclerosis/or exp myocardial ischemia/or exp myocardial reperfusion injury/or exp ischemia/(1370527)

  20. ((cardio* or cardiac or heart or coronary or myocard* or endocard* or pericard* or subendocard* transmural or ventricle or ventricular) adj2 (infarct* or ischem* or ischaem* or disease* or risk*)).tw. (601913)

  21. CV risk.tw. (2861)

  22. coronary heart disease.tw. (46791)

  23. AMI.tw. (16690)

  24. AMIs.tw. (518)

  25. (ST adj1 elevation).tw. (11552)

  26. (non-ST adj1 elevation).tw. (2851)

  27. acute MI.tw. (3003)

  28. (cardiovascular adj1 (mortality or morbidity)).tw. (19798)

  29. brain disease/or exp brain injury, chronic/or exp brain death/or exp cerebrovascular disorders/or exp hypoxia, brain/or exp ischemia/or exp intracranial embolism/or thrombosis/(514225)

  30. ((cerebro* or cerebral or cerebellar or cerebellum or brain or lacunar) adj2 (infarct* or ischem* or ichaem* or disease* or risk* or stroke* or embolism*)).tw. (97963)

  31. stroke*.tw. (205331)

  32. cerebrovascular disease*.tw. (17474)

  33. transient ischemic attack.tw. (6933)

  34. (cerebrovascular adj (mortality or morbidity)).tw. (359)

  35. 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 (1993955)

  36. 18 and 35 (2031)

  37. exp animals/not humans.sh. (4592045)

  38. 37 not 38 (1867)

Supplement 3: Risk of Bias of Studies Included in Meta-analysis

1 (Randomised controlled trials)

Reference (year) Random sequence generation Allocation concealment Blinding of participants and personnel Blinding of outcome assessment Incomplete outcome data Selective reporting Other bias
Bigardet al.36 (2005) Unclear Unclear Low Unclear Low Unclear Low
Dunn et al. 38(2013) High Low High Low Low Low Low
Fasset al.39 (2009) Low Low Low Low Low Low Low
Flooket al.40 (2012) Low Low Low Unclear Low Low Low
Howden et al.42 (2009) Low Unclear Low Low High Low Low
Kiljanderet al.44 (2010) Unclear Unclear Low Low Low Low Low
Kinoshita et al.45 (2011) Low Unclear Low Unclear Low Low Low
Richter et al.47 (2000) Unclear Unclear Low Unclear Low Unclear Low
Talley et al.50 (2001) Unclear Unclear Low Unclear Low Unclear Low

2 (Cohort studies)

Reference (year) Selection (max 4) Comparability (max 2) Intervention/Exposure (max 3) Total (max 9)
Representative of exposed cohort Selection of non-exposed cohort Ascertainment of exposure Outcome not at start Comparability Assessment of outcome Length of follow-up Adequacy of follow-up
Charlot et al.37 (2010) 1 1 1 1 2 1 1 1 9
Ho et al.24 (2009) 1 1 1 1 2 1 1 1 9
Kreutz et al.46 (2010) 1 1 1 1 2 1 1 1 9
Schmidt et al. 48 (2012) 1 1 1 1 2 1 1 1 9
Shah et al. 25 (2015) 1 1 1 1 2 1 1 0 8
Shih et al. 26 (2014) 1 1 1 1 2 1 1 1 9

2 (Case-control studies)

Reference (year) Selection (max 4) Comparability (max 2) Intervention/Exposure (max 3) Total (max 9)
Case definition adequate Representative of cases Selection of controls Definition of controls Comparability Ascertainment of exposure Same method of ascertainment for cases and controls Non-response rate
Valkhoffet al.52 (2011) 1 1 0 1 2 1 1 0 7

1. Randomised controlled trials: Cochrane tool for assessing risk of bias

Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.

2. Cohort studies/Case control studies: Newcastle-Ottawa quality assessment scale

Wells GA SB, O'Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of non-randomised studies in meta-analyses. Available from: https://www.ohro.ca/programs/clinical_epidemiology/oxford.asp

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